Salt Effects on the Thermodynamics of a Frameshifting RNA Pseudoknot under Tension

Naoto Hori; Natalia A. Denesyuk; D. Thirumalai

Recently, there is heightened interest in the biophysics of PK folding because it plays a crucial role in affecting the efficiency of −1 programmed ribosomal frameshifting (−1 PRF) [14] [15] [16] . Usually, proteins are synthesized when the ribosome reads the mRNA code in three nucleotide steps until the stop codon is reached. In −1 PRF, the open reading frame of mRNA being translated within the ribosome is programmed to be shifted by one nucleotide, and consequently, the mRNA becomes nonfunctional or produces an entirely different protein [5, [17] [18] [19] [20] . The downstream PK of the mRNA is a roadblock at the entrance to the mRNA channel on the ribosome, which impedes the translocation of the ribosome. The ribosome must unfold the PK, presumed to occur by exertion of mechanical force, to complete translocation. Because frameshifting efficiency could depend on how the PK responds to force, a number of single-molecule pulling experiments have focused on PKs [15, 21, 22] . Several factors could determine −1 PRF, as evidenced by the multitude of proposals based on many experimental studies [14, 15, [23] [24] [25] [26] [27] [28] . Nevertheless, given that ribosome translocation exerts mechanical force on the downstream mRNA, it is physically reasonable to assume that resistance of PK to force should at least be one factor determining the frameshifting efficiency [14, 29] .